# Development and validation of clinical outcome assessments in LGMD2A

> **NIH NIH R21** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $198,181

## Abstract

Summary:
The overall goal of this project is to develop reliable and valid clinical outcome assessments (COAs) for limb
girdle muscular dystrophy 2A (LGMD2A) to hasten therapeutic development. LGMD2A is an autosomal
recessive form of LGMD due to a loss of function in muscle structural gene CAPN3. This loss of function leads
to progressive weakness of the shoulder and hip girdle muscles and therefore progressive disability, including
loss of ambulation or the ability to maintain a job. There are no FDA approved treatments for LGMD2A, which
represents a large unmet medical need. LGMD2A is amenable to gene replacement therapies; and in recent
years, a systemic gene therapy has been approved for spinal muscular atrophy, and is in development for
LGMD2E. At least three companies have gene-targeted therapies in development for LGMD2A – creating a
situation where therapeutic development has outstripped our ability to prepare for clinical trials. The rationale
for this study is that defining a core set of COAs for LGMD2A which are reliable, related to key areas of
LGMD2A disease impact, and responsive to disease progression, and determining the size of change in the
COAs which would be clinically meaningful would hasten therapeutic development and allow for properly
powered clinical trials. We propose the following Specific Aims: 1) To define a common set of pelvic and
shoulder girdle COAs, and COAs useful for capturing phenotypic diversity; 2) To determine the sensitivity to
longitudinal disease progression of our COAs; and 3) To refine clinical trial strategies based on baseline and
longitudinal phenotypic characteristics. To achieve our aims, we plan to leverage an existing LGMD Clinical
Research Network to conduct a 12 month longitudinal observational study of 50 clinically affected and
genetically defined LGMD2A indivdiuals at eight sites on our LGMD Research Network. We hypothesize that
COAs representing the major areas of shoulder and pelvic girdle functional burden will be amenable to multi-
site training, reliable, related to patient-identified areas of disease impact, and useful for power and sample
size planning for forthcoming clinical trials. In addition, we hypothesize that certain baseline clinical
characteristics related to age, functional status, or mutation may be useful for refining trial planning strategies.
At the completion of this study, we will have: defined the phenotypic variation across LGMD2A; determined
which COAs are most appropriate for therapeutic trials; and established the variability in these COAs for power
and sample size planning. Given the significant progress in therapeutic development for LGMD2A, the
development of appropriate COAs for this population is an urgent need.

## Key facts

- **NIH application ID:** 10145831
- **Project number:** 5R21TR003184-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Nicholas Elwood Johnson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $198,181
- **Award type:** 5
- **Project period:** 2020-04-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145831

## Citation

> US National Institutes of Health, RePORTER application 10145831, Development and validation of clinical outcome assessments in LGMD2A (5R21TR003184-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145831. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*